Pelota–HBS1-like protein complex (PELO–HBS1L complex)

The **Pelota–HBS1-like protein complex (PELO–HBS1L complex)** is a conserved eukaryotic ribosome rescue machine, crucial for resolving stalled ribosomes at the 3' end of mRNAs and maintaining the fidelity of translation[2][4][5][8]. The complex consists of the RNA-binding protein Pelota and the GTPase HBS1L; together, they recognize and dissociate stalled ribosomes, activate the No-Go Decay pathway, and initiate cellular stress responses including the unfolded protein response when functionally impaired[1][7][8]. The interaction is essential for cell proliferation, embryo brain and cerebellum development, and spermatogenesis[2][4]. In cancer biology, loss or inhibition of the PELO–HBS1L complex or its regulatory partners can produce synthetic lethality, especially in tumors with chromosomal instability or superkiller complex (SKIc) deficiency[1][3]. No drug currently targets this complex clinically, but apogossypol-derived ligands disrupting the protein-protein interface have shown experimental promise[3]. Safety concerns arise due to its fundamental role in translation and cell cycle control, posing challenges for targeting outside selective cancer contexts.

Other names

Pelota-HBS1L complexPelo/Hbs1l complexPelota/HBS1L ribosome rescue complexDom34-Hbs1 (yeast orthologs)PELO-HBS1L interface

Experimental: Protein-protein interaction (PPI) inhibition—small molecules disrupt the PELO–HBS1L interface, leading to synthetic lethality in cancer cells dependent on ribosome rescue. No approved mechanism for established drugs.